Project Description: The overall objective of this proposal is to develop a novel method for detecting early evidence of Alzheimer's disease (AD) based on optical imaging of the retina. AD is a debilitating neurodegenerative disease with an increasing societal burden in the U.S. as the population ages. Although deposition of amyloid plaques in brain tissue is the clearest pathological indicator of AD, no clinical diagnostics currently exist for its detection until cognitive impairment can be recognized. AD patients have been known to complain of decrease in visual acuity, leading several investigations to seek to link retinal features with early onset of the disease. The state-of-the-art technology in measurement of retinal structure is spectral domain optical coherence tomography (SDOCT). However, while SDOCT can resolve histological layers, most clinical implementations lack the resolution to measure cellular features. We have shown that angle-resolved low coherence interferometry (a/LCI), a light scattering method that incorporates the depth resolution of OCT, can obtain morphological measurements of esophageal epithelial cells, enabling in vivo early detection of dysplasia in Barrett's Esophagus patients. We have also recently demonstrated that a/LCI can detect pathological changes in the organization of retinal layers in a mouse model of degenerative retinal disease. We now propose to apply a/LCI to the early detection of amyloid plaques in a mouse model of AD. Our benchtop a/LCI imaging system includes co-registered OCT measurements which enable us to identify light scattering changes from specific histological layers as well as link any alterations in layer morphology in OCT imaging with the presence of amyloid plaques. Here we seek to conduct an R21 exploratory project that applies a/LCI to characterize amyloid plaques using retinal light scattering measurements and formulate quantitative biomarkers that predict the onset and progression of plaque formation. In this project, (1) we will characterize the animal model using the integrated a/LCI & OCT system, (2) we will advance our a/LCI & OCT system to enable in vivo studies of mice retina and (3) apply the system to a detailed time course study of a murine AD model to characterize the changes in light scattering features as a function of disease progression. Upon successful completion of this exploratory research study, there will be justification to pursue development of a clinical a/LCI device for application to humans.